ArticleThe Journal of pharmacology and experimental therapeutics2013
Hepatocyte nuclear factor 1 regulates the expression of the organic cation transporter 1 via binding to an evolutionary conserved region in intron 1 of the OCT1 gene.
Article in The Journal of pharmacology and experimental therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Cortisol drives pregnancy-associated induction of hepatic organic anion transporter 2, sodium/taurocholate cotransporting polypeptide, and organic cation transporter 1 in HepaRG cells through glucocorticoid receptor-, hepatocyte nuclear factor 1 alpha-, and hepatocyte nuclear factor 4 alpha-dependent signaling.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Distinct Roles of Common Genetic Variants and Their Contributions to Diabetes: MODY and Uncontrolled T2DM.Biomolecules · 2025Review
- Regulation of Drug Transport Proteins-From Mechanisms to Clinical Impact: A White Paper on Behalf of the International Transporter Consortium.Clinical pharmacology and therapeutics · 2022Review
- Actionable secondary findings following exome sequencing of 836 non-obstructive azoospermia cases and their value in patient management.Human reproduction (Oxford, England) · 2022Article
- Organic Cation Transporter (OCT/OCTN) Expression at Brain Barrier Sites: Focus on CNS Drug Delivery.Handbook of experimental pharmacology · 2021Article
- Effects of a Common Eight Base Pairs Duplication at the Exon 7-Intron 7 Junction on Splicing, Expression, and Function of OCT1.Frontiers in pharmacology · 2021Article
- Influence of YES1 Kinase and Tyrosine Phosphorylation on the Activity of OCT1.Frontiers in pharmacology · 2021Article
- Novel insights into the organic solute transporter alpha/beta, OSTα/β: From the bench to the bedside.Pharmacology & therapeutics · 2020Review
- Regulation Mechanisms of Expression and Function of Organic Cation Transporter 1.Frontiers in pharmacology · 2020Review
- Enhanced Intestinal Permeability and Plasma Concentration of Metformin in Rats by the Repeated Administration of Red Ginseng Extract.Pharmaceutics · 2019Article
- Impact of Promoter Polymorphisms on the Transcriptional Regulation of the Organic Cation Transporter OCT1 (SLC22A1).Journal of personalized medicine · 2018Article
- ABC transporter polymorphisms are associated with irinotecan pharmacokinetics and neutropenia.The pharmacogenomics journal · 2018Article
- OCT1 genetic variants are associated with postoperative morphine-related adverse effects in children.Pharmacogenomics · 2017Article
- Carriers of genetic variants in the HNF1A gene are more common among dead opioid addicts than among living addicts.European journal of clinical pharmacology · 2016Article
- Development of Human Membrane Transporters: Drug Disposition and Pharmacogenetics.Clinical pharmacokinetics · 2016Review
- Role of SLC22A1 polymorphic variants in drug disposition, therapeutic responses, and drug-drug interactions.The pharmacogenomics journal · 2015Review
- Article
- Sex-differences in renal expression of selected transporters and transcription factors in lean and obese Zucker spontaneously hypertensive fatty rats.Journal of diabetes research · 2015Article
- Genetic variants in transcription factors are associated with the pharmacokinetics and pharmacodynamics of metformin.Clinical pharmacology and therapeutics · 2014Article
- PharmGKB summary: very important pharmacogene information for SLC22A1.Pharmacogenetics and genomics · 2014Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
The organic cation transporter 1 (OCT1), also known as solute carrier family 22 member 1, is strongly and specifically expressed in the human liver. Here we show that the hepatocyte nuclear factor 1 (HNF1) regulates OCT1 transcription and contributes to the strong, liver-specific expression of OCT1. Bioinformatic analyses revealed strong conservation of HNF1 binding motifs in an evolutionary conserved region (ECR) in intron 1 of the OCT1 gene. Electrophoretic mobility shift and chromatin immunoprecipitation assays confirmed the specific binding of HNF1 to the intron 1 ECR. In reporter gene assays performed in HepG2 cells, the intron 1 ECR increased SV40 promoter activity by 22-fold and OCT1 promoter activity by 13-fold. The increase was reversed when the HNF1 binding sites in the intron 1 ECR were mutated or the endogenous HNF1α expression was downregulated with small interfering RNA. Following HNF1α overexpression in Huh7 cells, the intron 1 ECR increased SV40 promoter activity by 11-fold and OCT1 promoter activity by 6-fold. Without HNF1α overexpression, the increases were only 3- and 2-fold, respectively. Finally, in human liver samples, high HNF1 expression was significantly correlated with high OCT1 expression (r = 0.48, P = 0.002, n = 40). In conclusion, HNF1 is a strong regulator of OCT1 expression. It remains to be determined whether genetic variants, disease conditions, or drugs that affect HNF1 activity may affect the pharmacokinetics and efficacy of OCT1-transported drugs such as morphine, tropisetron, ondansetron, tramadol, and metformin. Beyond OCT1, this study demonstrates the validity and usefulness of interspecies comparisons in the discovery of functionally relevant genomic sequences.
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